This K01 application responds to PA-10-056, and is intended to obtain support and protected time for Dr. Rajeev I. Desai (PI) to gain extensive supervised research training and experience in all aspects of intravenous (IV) self-administration methodology in non-human primates (NHP). The project is designed to systematically allow the PI to acquire necessary skills and experience to independently and expertly study the reinforcing effects of stimulant and other addictive drugs, and to couple this methodology with concurrent in vivo microdialysis to measure related neurochemical activity. The support provided by the K01 award will ultimately allow the PI to: a) develop a comprehensive program of highly translational neurochemical and behavioral studies to directly address the public health concern of stimulant addiction and the development of medications for its treatment; and b) acquire the tools necessary to independently continue and expand this line of research through R01 funding mechanisms. The aims of this project are designed to optimize the PI's training experience through a systematic series of experiments evaluating IV cocaine and nicotine self- administration behavior under simple and complex schedules of reinforcement. The PI next will couple his existing expertise with in vivo microdialysis techniques to his newly acquired behavioral skills to measure changes in striatal dopamine levels produced by cocaine and nicotine during IV self-administration performance under different schedule conditions. Finally, studies will be conducted to determine whether nicotinic agonist-based candidate medications attenuate reinforcing and neurochemical effects of self- administered nicotine or cocaine. The proposed research in this project will establish the PI as a well-trained and independent young scientist who is qualified to conduct highly translational addiction research in NHP. In addition, the planned studies may lead to the further development of promising novel nicotinic-based pharmacotherapy to help combat the scourge of stimulant addiction that plagues our public health. PUBLIC HEALTH RELEVANCE: Translational behavioral and neurochemical methodologies are an integral part of drug addiction research methodology, and there is a clear need for trained scientists who are qualified to conduct this type of multi- dimensional work in nonhuman primates. This project is designed to systematically provide a young investigator with intensive supervised research training to directly measure the reinforcing effects of addictive drugs and their associated neurochemical changes in highly translational procedures. The proposed research will lead to a greater understanding of neurochemical mechanisms in psychomotor stimulant addiction, and may identify novel nicotinic targets to help combat this public health concern.